Erythropoietin (EPO) is a hematopoietic growth factor that stimulates proliferation and differentiation of erythroid precursor cells and is also known to exert neurotrophic activity in the central nervous system (CNS). However, little is known about expression of EPO and EPO receptor (EPOR) in human CNS tissues. In the present study, we investigated the effects of proinflammatory cytokines on EPO and EPOR expression in highly purified cultures of human neurons, astrocytes, microglia, and oligodendrocytes using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). EPO mRNA was demonstrated only in human astrocytes, while EPOR expression was found in human neurons, astrocytes, and microglia. Neither EPO nor EPOR expression was found in oligodendrocytes. In human astrocytes, EPO mRNA and secreted EPO protein levels were downregulated after exposure to proinflammatory cytokines (IL-1beta, IL-6, or TNF-alpha). In human neurons, TNF-alpha treatment markedly increased EPOR expression. These results suggest that proinflammatory cytokines regulate expression of EPO and EPOR in human neurons, astrocytes, and microglia and further facilitate interactions among different cell types in the human CNS.